2x1d

The crystal structure of mature acyl coenzyme A:isopenicillin N acyltransferase from Penicillium chrysogenum

spinqualitylabelsall models 2x1d, resolution 1.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2x1d is a 4 chain structure with sequence from Penicillium chrysogenum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.64Å Ligands: ACT, CL, CSD, D1D, GOL, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AATA_PENCH Isopenicillin-N N-acyltransferase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:1368505, PubMed:2110531, PubMed:2120195). AatA catalyzes the exchange of the alpha-aminoadipyl side chain of isopenicillin N for phenylacetic acid to yield penicillin (PubMed:1368505, PubMed:2110531, PubMed:2120195). This step occurs in the peroxisomal matrix and the penM and paaT transporters are involved in the isopenicillin N and phenylacetic acid import into the peroxisome, respectively (PubMed:23053082). The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase aatA to yield penicillin in the peroxisomal matrix (Probable) (PubMed:1368505). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Penicillium chrysogenum Acyl coenzyme A:isopenicillin N acyltransferase (AT) performs the last step in the biosynthesis of hydrophobic penicillins, exchanging the hydrophilic side chain of a precursor for various hydrophobic side chains. Like other N-terminal nucleophile hydrolases AT is produced as an inactive precursor that matures upon posttranslational cleavage. The structure of a Cys103Ala precursor mutant shows that maturation is autoproteolytic, initiated by Cys103 cleaving its preceding peptide bond. The crystal structure of the mature enzyme shows that after autoproteolysis residues 92-102 fold outwards, exposing a buried pocket. This pocket is structurally and chemically flexible and can accommodate substrates of different size and polarity. Modeling of a substrate-bound state indicates the residues important for catalysis. Comparison of the proposed autoproteolytic and substrate hydrolysis mechanisms shows that in both events the same catalytic residues are used, but that they perform different roles in catalysis. Structures of an isopenicillin N converting Ntn-hydrolase reveal different catalytic roles for the active site residues of precursor and mature enzyme.,Bokhove M, Yoshida H, Hensgens CM, van der Laan JM, Sutherland JD, Dijkstra BW Structure. 2010 Mar 10;18(3):301-8. PMID:20223213 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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